Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Na+-K+-2Cl- cotransporters are important in renal salt reabsorption and in salt secretion by epithelia. They are also essential in maintenance and regulation of ion gradients and cell volume in both epithelial and nonepithelial cells. Expression of Na+-K+-2Cl- cotransporters in brain tissues is high; however, little is known about their function and regulation in neurons. In this study, we examined regulation of the Na+-K+-2Cl- cotransporter by the excitatory neurotransmitter glutamate. The cotransporter activity in human neuroblastoma SH-SY5Y cells was assessed by bumetanide-sensitive K+ influx, and protein expression was evaluated by Western blot analysis. Glutamate was found to induce a dose- and time-dependent stimulation of Na+-K+-2Cl- cotransporter activity in SH-SY5Y cells. Moreover, both the glutamate ionotropic receptor agonist N-methyl-D-aspartic acid (NMDA) and the metabotropic receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) significantly stimulated the cotransport activity in these cells. NMDA-mediated stimulation of the Na+-K+-2Cl- cotransporter was abolished by the selective NMDA-receptor antagonist (+)-MK-801 hydrogen maleate. trans-ACPD-mediated effect on the cotransporter was blocked by the metabotropic receptor antagonist (+)-alpha-methyl-(4-carboxyphenyl)glycine. The results demonstrate that Na+-K+-2Cl- cotransporters in neurons are regulated by activation of both ionotropic and metabotropic glutamate receptors.
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PMID:Stimulation of Na+-K+-2Cl- cotransporter in neuronal cells by excitatory neurotransmitter glutamate. 973 Sep 61

Apoptosis and aging share common mechanisms in oxidative stress and mitochondrial involvement. Treatment of cultured neuroblastoma cells with a radical initiator induced apoptosis; raise in hydrogen peroxide and release of cytochrome c from mitochondria preceded collapse of mitochondrial potential and cell death. In rat hepatocytes treated with adriamycin incubation with exogenous Coenzyme Q10 counteracted the drug-induced increase of hydrogen peroxide and the fall of the mitochondrial potential, thus demonstrating the quinone antioxidant effect. Complex I activity and its rotenone sensitivity decreased in brain cortex non-synaptic mitochondria from old rats; a 5 kb mitochondrial DNA deletion was found only in the old rats. A similar behavior was found in human platelets from old individuals. The postulated energy decline was confirmed by the inhibitor sensitivities of platelet aggregation and lactate production. The lack of the 5 kb deletion in platelets throws doubts on mitochondrial DNA lesions as the only causes of mitochondrial dysfunction in aging.
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PMID:Oxidative stress, antioxidant defences and aging. 991 19

The present investigation demonstrates distinct patterns of activation for antioxidant/electrophile-responsive elements (ARE/EpREs) in cells of neuronal versus hepatic origin suggesting the possibility of cell-/tissue-specific signaling pathways and/or transcription factors required for ARE/EpRE activation. The ARE/EpRE is a cis-acting regulatory element found in 5'-flanking regions of numerous genes including NAD(P)H:quinone oxidoreductase (QR) and glutathione S-transferases. Insomuch as ARE/EpRE activation has been studied primarily in hepatoma cell lines there is little information on how these responsive elements and corresponding genes are regulated in brain. ARE/EpRE-reporter constructs were transiently transfected into IMR-32 human neuroblastoma cells. Activation of ARE/EpRE sequences by tert-butylhydroquinone (tBHQ), a redox-cycling compound, in IMR-32 cells (20- to 30-fold) is dramatically different from the minimal response seen in HepG2 human hepatoma cells (2- to 3-fold). beta-napthoflavone, an ARE/EpRE inducer in HepG2 cells, as well as the oxidants hydrogen peroxide and tert-butyl hydroperoxide did not induce the ARE/EpRE in IMR-32 cells. In addition, we show that the core sequence containing a complete 5' palindrome is necessary for maximal activation of the ARE/EpRE in IMR-32 cells. Mutations within this palindromic sequence decrease basal level expression and block induction by tBHQ but not phorbol 12-myristate 13-acetate. Furthermore, activation of the hQR-ARE/EpRE by tBHQ correlates with induction of endogenous QR activity in IMR-32 neuroblastoma cells (15-fold). Thus, elucidating the mechanism of ARE/EpRE activation in this human neuroblastoma cell line may identify unknown transcription factors or signal transduction cascades regulating ARE/EpRE-driven gene expression.
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PMID:Activation of antioxidant/electrophile-responsive elements in IMR-32 human neuroblastoma cells. 1004 3

The aim of the study was to determine the major source and extent of metal pollution in a residential area of Greater Calcutta. In this area approximately 50,000 people reside in the vicinity of a lead factory that produces lead ingots and lead alloys. Many people, especially children, are affected by lead toxicity. Soils, waters, road dust, leaf dust, leaves and pond sediments were sampled in and around the factory area. Aliquots of the samples were mineralized with nitric acid and hydrogen peroxide in a microwave system. Lead and 19 other elements were quantified in the digests by inductively coupled plasma mass spectrometry. The performance of the procedure was confirmed by analyzing NBS-BCR standard reference soil, leaves, sediment samples. The soils are highly contaminated not only with lead (4.7%), but also with Cd (0.08%), Ag (0.001%), Cu (0.02%), Zn (1.0%), As (1.0%), Mo (0.003%), Sn (0.003%) and Hg (0.03%) (metal concentrations given in parentheses are maximum). Moving away from the smelter, most of metal concentrations, especially Pb, As, Mo, Cu, Hg, Zn, Cd, Sn and Ag, decreased exponentially over increasing distance. In the residential areas near the smelter, notably to the west side of the factory, metal concentrations significantly breached the threshold trigger values set in India by the Central Pollution Control Board (CPCB). Particulate materials from the smelter stack appear to contaminate soils up to at least 0.5 km. However, abnormally high metal levels in the immediate smelter area may be due to primarily fugitive emissions. The surface waters are only contaminated by arsenic ranges from 0.05 to 13.5 mg/l, but the ground water is currently not polluted by lead and arsenic. An appropriate treatment plant with some intervention measures should be taken to save the locality.
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PMID:Determination of lead and other metals in a residential area of greater Calcutta. 1023 82

Basic fibroblast growth factor (bFGF) has been reported to have neuroprotective properties following excitotoxic, metabolic, and oxidative insults. We report here that another FGF family member, FGF-8 is able to protect rat hippocampal cultures from oxidative stress. The b isoform of FGF-8 protected hippocampal cultures from hydrogen peroxide with an EC50 of approximately 25 ng/ml. In a time course study, using pre-, co-, post-treatment paradigms, we report that bFGF and FGF-8b were neuroprotective when added as a pre-treatment, co-treatment, and even at 2 h post-insult. Using neuronal enriched cultures, we demonstrate that bFGF and FGF-8b neuroprotection partially results from a direct action of the growth factors on neurons. The direct action on neurons may work in concert with normal and FGF-stimulated glial secretion products to give the full FGF protective effect. FGF-8b showed maximal protection at 50 ng/ml, whereas bFGF showed maximal protection at 10 ng/ml. Despite requiring higher concentrations to elicit protection, FGF-8b is able to attain levels of protection equivalent to that of bFGF (attenuation of 75-80% of hydrogen peroxide induced death). We also report that bFGF and FGF-8b are able to protect the human neuroblastoma cell line, SK-N-MC, from peroxide-induced LDH release by 50%. From these studies, we conclude that FGF-8b is another member of the FGF family which may show in vivo efficacy for the treatment of oxidative insults, such as stroke.
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PMID:Fibroblast growth factor-8 protects cultured rat hippocampal neurons from oxidative insult. 1035 May 62

Free radicals are involved in neuronal damage. Bifemelane hydrochloride has been reported to protect neural tissues against ischemic damage and age-related neurodegeneration. We examined the protective effects of bifemelane HCl and the relation between its effectiveness and free radical formation in hydrogen peroxide (H2O2)-induced cytotoxicity using cultured rat neuroblastoma cell line (B50). Cytotoxicity was examined by using the lactate dehydrogenase (LDH) assay and cell viability by the WST-1 assay. H2O2 reduced the survival of B50 cells in a dose-dependent manner, and treatment of these cells with 75 microM or 100 microM H2O2 reduced their viability by 50% relative to the control group. B50 cells were treated with 5 or 10 microM bifemelane for 2 days followed by treatment with 75 microM or 100 microM H2O2. H2O2 cytotoxicity was reduced by pretreatment with bifemelane. We also examined the effect of bifemelane on lipid peroxide formation in B50 cells using thiobarbituric acid reactive substances assay. Pretreatment of B50 cells with 10 microM bifemelane for 2 days reduced lipid peroxide formation to approximately 54% of the control group. Our results suggest that bifemelane hydrochloride provides a protective effect against H2O2 cytotoxicity partly due to its anti-oxidative properties.
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PMID:Bifemelane hydrochloride protects against cytotoxicity of hydrogen peroxide on cultured rat neuroblastoma cell line. 1040 25

Widespread cerebral deposition of a 40-43-amino acid peptide called the amyloid beta-protein (Abeta) in the form of amyloid fibrils is one of the most prominent neuropathologic features of Alzheimer's disease. Numerous studies suggest that Abeta is toxic to neurons by free radical-mediated mechanisms. We have previously reported that melatonin prevents oxidative stress and death of neurons exposed to Abeta. In the process of screening indole compounds for neuroprotection against Abeta, potent neuroprotective properties were uncovered for an endogenous related species, indole-3-propionic acid (IPA). This compound has previously been identified in the plasma and cerebrospinal fluid of humans, but its functions are not known. IPA completely protected primary neurons and neuroblastoma cells against oxidative damage and death caused by exposure to Abeta, by inhibition of superoxide dismutase, or by treatment with hydrogen peroxide. In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals. In contrast with other antioxidants, IPA was not converted to reactive intermediates with pro-oxidant activity. These findings may have therapeutic applications in a broad range of clinical situations.
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PMID:Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid. 1041 16

Ceramide is characterized as a second messenger of apoptosis induced by various agents such as tumor necrosis factor (TNF-alpha), Fas ligand, hydrogen peroxide, heat shock and ionizing radiation. In this study, we investigated the mechanism of ceramide-induced apoptosis using a human neuroblastoma cell line, SK-N-MC. N-Acetyl-sphingosine (C2-ceramide), a cell-permeable ceramide analogue, was able to induce apoptosis in SK-N-MC cells as estimated by DNA fragmentation and chromatin condensation. C2-ceramide-induced DNA fragmentation was blocked by caspase inhibitor (Z-Asp-CH(2)-DCB). An increase in caspase-3 (CPP32)-like protease activity was evident during C2-ceramide-induced apoptosis, suggesting that caspases are involved in this apoptosis. Moreover, enzymatic cleavage of VDVAD-AFC and LEHD-AFC (specific substrates for caspase-2 and -9, respectively) was increased by treatment with C2-ceramide. To elucidate which types of caspase are activated in C2-ceramide-treated cells, we performed Western blot analysis using antibodies against each isoform. Both proforms of caspase-2 and -3 were decreased in response to C2-ceramide in a time-dependent manner. Mitochondrial cytochrome c is also time-dependently released into the cytosol in response to treatment with C2-ceramide. Addition of cytochrome c into the S-100 fractions prepared from SK-N-MC cells could activate caspase-2 in cell-free systems. These results suggest the possibility that cytochrome c released to the cytosol can activate caspases (caspase-9, -3, and -2) during C2-ceramide-induced apoptosis of SK-N-MC cells.
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PMID:Possible involvement of cytochrome c release and sequential activation of caspases in ceramide-induced apoptosis in SK-N-MC cells. 1059 Mar 15

Human neuroblastoma CHP100 cells were forced into apoptosis (programmed cell death, PCD) or necrosis by treatment with calcium chloride or sodium nitroprusside (a nitric oxide donor), respectively. Cellular luminescence, a marker of membrane lipid peroxidation, was increased by calcium but not by nitroprusside, and reached a maximum of 4-fold the control value 2 hours after treatment. The increase in luminescence was paralleled by increased 5-lipoxygenase (up to 250% of the control value) and decreased catalase (down to 50%) activity within the same time window. Consistently, incubation of CHP100 cells with inhibitors of 5-lipoxygenase (5,8,11,14-eicosatetraynoic acid and MK886) reduced light emission and PCD, whereas inhibition of catalase by 3-amino-1, 2,4-triazole enhanced both processes. Treatment of CHP100 cells with retinoic acid or cisplatin, unrelated PCD inducers reported to activate the lipoxygenase pathway, also gave enhanced light emission parallel to PCD increase. Altogether, these results suggest that cellular luminescence is an early marker of apoptotic, but not necrotic, program(s) involving generation of hydrogen peroxide and activation of 5-lipoxygenase.
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PMID:The early phase of apoptosis in human neuroblastoma CHP100 cells is characterized by lipoxygenase-dependent ultraweak light emission. 1060 Apr 93

alpha-Synuclein is a key component of Lewy bodies found in the brains of patients with Parkinson's disease and two point mutations in this protein, Ala53Thr and Ala30Pro, are associated with rare familial forms of the disease. Several lines of evidence suggest the involvement of oxidative stress in the pathogenesis of nigral neuronal death in Parkinson's disease. In the present work we studied the effects of changes in the alpha-synuclein sequence on the susceptibility of cells to reactive oxygen species. Human dopaminergic neuroblastoma SH-SY5Y cells were stably transduced with various isoforms of alpha-synuclein and their survival following exposure to hydrogen peroxide or to the dopaminergic neurotoxin MPP(+) was assessed. Cells expressing the two point mutant isoforms of alpha-synuclein were significantly more vulnerable to oxidative stress, with the Ala53Thr engineered cells faring the worst. In addition, cells expressing C-terminally truncated alpha-synuclein, particularly the 1-120 residue protein, were more susceptible than control beta-galactosidase engineered cells. The present experiments indicate that point mutations and C-terminal truncation of alpha-synuclein exaggerate the susceptibility of dopaminergic cells to oxidative damage. Thus, these observations provide a pathogenetic link between alpha-synuclein aberrations and a putative cell death mechanism in Parkinson's disease.
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PMID:Enhanced vulnerability to oxidative stress by alpha-synuclein mutations and C-terminal truncation. 1079 59


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